Thyroglobulin (Tg) is a large, specialized glycoprotein produced almost exclusively by the thyroid gland, the small, butterfly-shaped organ located at the base of the neck. This protein serves a foundational purpose in the thyroid’s structure and hormone production mechanism. The presence of Tg is a direct indicator of thyroid tissue activity, whether that tissue is healthy or cancerous. Its measurement in the blood is an important tool in medical diagnostics.
The Primary Biological Function
The main function of thyroglobulin is to act as the biological scaffold for synthesizing and storing the body’s thyroid hormones, specifically thyroxine (T4) and triiodothyronine (T3). The protein is synthesized by follicular cells and secreted into the follicular lumen, a central cavity filled with colloid. Tg is abundant in this colloid, making up approximately half of the thyroid gland’s total protein content.
The synthesis of T4 and T3 relies on iodination, a process where iodine atoms attach to specific tyrosine residues on the Tg molecule. The protein provides multiple sites for this attachment, acting as a large storage unit for iodine and the partially formed hormones. When the body requires T4 and T3, thyroid cells reabsorb the Tg from the colloid. Once inside the cell, the Tg molecule is cleaved by enzymes in a process called proteolysis, which releases the active thyroid hormones into the bloodstream.
How Thyroglobulin is Measured
Serum thyroglobulin levels are measured using a simple blood test that quantifies the amount of the protein circulating in the bloodstream. In healthy individuals with sufficient iodine intake, the normal reference range for Tg is typically between 3 and 40 nanograms per milliliter (ng/mL) of blood. This baseline level reflects the small amount of the protein that naturally leaks from the thyroid gland into the circulation.
Elevated Tg levels can occur in various conditions not related to cancer, as any process that stimulates thyroid tissue or causes cell damage can increase the protein’s release. For instance, an overactive thyroid gland, a condition known as hyperthyroidism, often results in higher Tg levels due to increased hormone production activity. Thyroiditis, an inflammation of the gland, can also elevate Tg as damaged cells release stored protein into the blood. A non-cancerous enlargement of the thyroid gland, called a goiter, will also generally lead to higher circulating Tg levels because a larger volume of thyroid tissue is present.
Because different laboratory methods and equipment can yield varied results, medical guidelines recommend that a patient’s Tg levels be monitored consistently using the same testing assay over time. This approach ensures that any change in the Tg value is a true biological shift.
The Role in Thyroid Cancer Monitoring
The most recognized use of the Tg test is its application as a surveillance marker following treatment for differentiated thyroid cancer, which includes the common papillary and follicular types. These cancer cells, like normal thyroid cells, retain the ability to produce and secrete thyroglobulin. Following a total thyroidectomy—the surgical removal of the entire thyroid gland—Tg levels should ideally become undetectable or extremely low.
A very low or undetectable serum Tg level in a patient who has had their thyroid removed suggests that the treatment was successful and there is no residual cancer or normal thyroid tissue remaining.
If Tg levels remain detectable or begin to rise over time, it provides an early warning sign of potential cancer recurrence or metastasis. A rising Tg indicates that cells capable of producing the protein are growing somewhere in the body. To enhance the sensitivity of this monitoring, a physician may order a “stimulated” Tg test, often by administering recombinant human Thyroid-Stimulating Hormone (TSH).
TSH causes any remaining thyroid tissue, including cancer cells, to become more active and produce more Tg, making even small amounts of residual disease easier to detect. For patients on thyroid hormone replacement therapy, a Tg level consistently below 0.1 to 0.2 ng/mL is generally associated with a very low risk of recurrence. Conversely, a level greater than 10 ng/mL in a patient without a thyroid gland suggests a significant risk of residual or recurrent disease, prompting further investigation.
Understanding Anti-Thyroglobulin Antibodies
In addition to measuring the thyroglobulin protein itself, physicians must simultaneously test for the presence of Anti-Thyroglobulin Antibodies (TgAb). These are autoantibodies, proteins produced by the immune system that mistakenly recognize and target the body’s own Tg. TgAb are found in a significant portion of patients with differentiated thyroid cancer, with prevalence estimates ranging from 20 to 30 percent.
The presence of these antibodies introduces a complication in the measurement of serum Tg. When TgAb are present, they bind to the thyroglobulin protein in the blood sample, which can interfere with the standard laboratory assays used to measure Tg. This interference often leads to a falsely low or even undetectable Tg result, potentially masking the presence of recurrent cancer.
The presence of TgAb complicates clinical monitoring. Testing for TgAb is mandatory because a falsely low Tg measurement can mislead results. If TgAb are detected, specialized testing methods, such as mass spectrometry, may be used to provide a more accurate Tg measurement that is less susceptible to antibody interference.